Elevated oxygen consumption rate in response to acute low-glucose stress: Metformin restores rate to normal level.

Cardiovascular disease (CVD) continues to be the leading cause of mortality among all age demographics in the United States, with the highest occurrence in populations aged 65 and older. Glucose levels, particularly hyperglycemia, are associated with the premature onset of age-related diseases including CVD. A major challenge in the treatment of elderly patients with chronically elevated blood glucose is the frequency of hypoglycemic episodes. Molecular mechanisms of hypoglycemia remain unclear, but are associated with premature onset of age-related-diseases. Here we report a mitochondrial metabolic profile assessing short-term (up to six hours) and longer-term (12-24h) durations of low-glucose stress. We observed that the anti-diabetic biguanide and mitochondrial complex I inhibitor, metformin, can lower and restore the elevated oxygen consumption rate during shorter-term glucose stress to levels similar to that of cells cultured in normal glucose. This effect appears, in part, to involve activation of the 5' AMP-activated protein kinase (AMPK).